3JQ4

The structure of the complex of the large ribosomal subunit from D. Radiodurans with the antibiotic lankacidin

Summary for 3JQ4

• Entry DOI: 10.2210/pdb3jq4/pdb
• Related: 1NKW
• Descriptor: 23S ribosomal RNA, 5S ribosomal RNA, N-[(1S,2R,3E,5E,7S,9E,11E,13S,15R,19R)-7,13-dihydroxy-1,4,10,19-tetramethyl-17,18-dioxo-16-oxabicyclo[13.2.2]nonadeca-3,5,9,11-tetraen-2-yl]-2-oxopropanamide (3 entities in total)
• Functional Keywords: ribosome structure, antibiotics, lankacidin, lankamycin, protein synthesis, inhibitors, synergism, macrolide, rna
• Biological source: Deinococcus radiodurans; More
• Total number of polymer chains: 2
• Total formula weight: 971894.31

Authors

Auerbach-Nevo, T.,Mermershtain, I.,Davidovich, C.,Bashan, A.,Rozenberg, H.,Yonath, A. (deposition date: 2009-09-06, release date: 2010-09-08, Last modification date: 2023-11-01)

Primary citation

Auerbach, T.,Mermershtain, I.,Davidovich, C.,Bashan, A.,Belousoff, M.,Wekselman, I.,Zimmerman, E.,Xiong, L.,Klepacki, D.,Arakawa, K.,Kinashi, H.,Mankin, A.S.,Yonath, A.
The structure of ribosome-lankacidin complex reveals ribosomal sites for synergistic antibiotics
Proc.Natl.Acad.Sci.USA, 107:1983-1988, 2010

PubMed Abstract: Crystallographic analysis revealed that the 17-member polyketide antibiotic lankacidin produced by Streptomyces rochei binds at the peptidyl transferase center of the eubacterial large ribosomal subunit. Biochemical and functional studies verified this finding and showed interference with peptide bond formation. Chemical probing indicated that the macrolide lankamycin, a second antibiotic produced by the same species, binds at a neighboring site, at the ribosome exit tunnel. These two antibiotics can bind to the ribosome simultaneously and display synergy in inhibiting bacterial growth. The binding site of lankacidin and lankamycin partially overlap with the binding site of another pair of synergistic antibiotics, the streptogramins. Thus, at least two pairs of structurally dissimilar compounds have been selected in the course of evolution to act synergistically by targeting neighboring sites in the ribosome. These results underscore the importance of the corresponding ribosomal sites for development of clinically relevant synergistic antibiotics and demonstrate the utility of structural analysis for providing new directions for drug discovery.

PubMed: 20080686
DOI: 10.1073/pnas.0914100107

Experimental method

X-RAY DIFFRACTION (3.52 Å)